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New Chemotherapy Drug Gentler On Fertility, Tougher On Cancer

According to the National Cancer Institute 72,000 adolescents and young adults (ages 15 to 39) are diagnosed with cancer each year. The most prevalent types of cancer in this patient population include lymphoma, leukemia, testicular cancer, melanoma, breast, and cervical cancer.

Chemotherapy is the treatment of cancer with a regimen of one or more cytotoxic antineoplastic drugs. A broader use of the term encompasses any chemical treatment used to treat disease.

Chemotherapy may be administered with a curative intent in hopes of eradicating cancer by killing the affected cells which divide rapidly, or to prolong life by palliating associated symptoms. This classification of drugs is often used in conjunction with other treatments, such as radiation or surgery.

Chemotherapeutic agents are not exclusively used to treat cancer, but have a role in the treatment of ankylosing spondylitis (chronic inflammatory disease of the axial skeleton), multiple sclerosis, scleroderma, Crohn’s disease, and rheumatoid arthritis.

Unfortunately, traditional chemotherapy can harm other normal cells of the body found in the bone marrow and digestive tract. Decreased production of blood cells, immunosuppression, inflammation of the lining of the digestive tract, and alopecia (hair loss) are side effects of the potent treatment.

Several newer anticancer drugs are not as indiscriminately cytotoxic, and instead target the proteins abnormally expressed in cancer cells.

Some cancer treatments can affect reproductive health, causing temporary or permanent infertility in patients. In an effort to circumvent the potential negative impact on fertility and still retain hard-hitting, combative effects against cancer cells, Northwestern University Feinberg School of Medicine scientists designed a newer chemotherapy drug utilizing nanoparticles.

This approach of presenting the designer chemotherapy drug — an arsenic trioxide in nanoparticles called nanobins, which consisted of nano-size crystalline arsenic particles densely packed and encapsulated in a surreptitious fat bubble — is meant to infiltrate like a Trojan Horse.

The use of the fat bubble (liposome) allows a significant dose of arsenic to bombard the tumor, but at the same time prevent normal tissue exposure. The fat bubble easy accesses the environment of the growing tumor where it is more acidic, causing the nanobin to release the covertly carried chemo drug.

Packaging and delivering the active drug in this manner has the desired effect on the tumor cells but prevents damage to ovarian tissue, follicles, and eggs. When tested against lymphoma, it was found to be more potent than when administered in the traditional free form.

The research, published in PLOS ONE, outlined how the scientists, in addition to the new drug, designed a quick in vitro test used to predict the toxicity of a chemotherapy drug on fertility. This novel test can be easily utilized by both cancer drugs in development and preexisting to assess the influence of these treatments on fertility.

Teresa Woodruff, a co-principal investigator of the study — chief of fertility preservation at Northwestern University Feinberg School of Medicine, and a Thomas J. Watkins Memorial Professor of Obstetrics and Gynecology at Feinberg — explained the overall goal was to specifically create a smart drug that would not inadvertently cause sterility or ferotoxity (fertility toxicity).

Thomas O’Halloran, the other principal investigator — who serves as a director of both the Chemistry of Life Processes Institute and the Basic Sciences Division of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, a Morrison Professor of Chemistry in the Weinberg College of Arts and Sciences at Northwestern, and is Woodruff’s husband — collaborated on the research.

Together the couple created and tested the drug by intersecting their interests of her fertility preservation and his cancer drug development. O’Halloran has utilized a similar delivery vehicle in his research involving targeting metastatic breast and ovarian cancer tumors with arsenic trioxide nanobins.

Richard Ahn, the study’s lead author and a medical student at Feinberg in the MD-PhD program, coordinated the preclinical testing of the nanobins as a graduate student in O’Halloran’s lab.